1. Field of the Invention
The invention relates to certain heterobicyclic keto- and amino-acids, esters and amides of the formulae (I) and (II) as defined herein and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in treating diseases and conditions of mammalian subjects, including humans, which are characterized by reduced blood flow, reduced oxygen availability or reduced carbohydrate metabolism in the cardiovascular system of the subject; such conditions include ischaemic heart disease (particularly angina pectoris and myocardial infarction) and cardiac failure. The compounds are also useful in treating diseases involving defects in carbohydrate metabolism such as diabetes.
2. Description of the Prior Art
Chatelus, Ann. Chim., 4, 505-47 (1949); Chem. Abstr., 44, 1975c (1950); Comptes Rendus, 224, 1777-79 (1947) records the preparation of 2,3-dihydrobenzofuranglyoxylic acid and its ethyl ester; and ethyl 6-chromanylglyoxylic acid.
U.S. Pat. No. 4,029,811 and European patent application No. 8,742, published Mar. 19, 1980 disclose acylation of 2-ethylchroman and 2-ethyl-2,3-dihydrobenzofuran with ethyl chloroglyoxalate and aluminum chloride to provide the corresponding 2-ethyl-6-chromanylglyoxalate and 2-ethyl-2,3-dihydro-5-benzofuranglyoxalate esters, useful as chemical intermediates.
U.S. Pat. No. 4,138,397 discloses 2,3-dihydro-5-benzofuranylglycine useful as an intermediate in production of 6-[2-amino-(2,3-dihydro-5-benzofuranyl)acetamido]-penicillin and derivatives.
The prior art does not disclose any medical use for the compounds of the instant invention, nor has any use been proposed for them, except as chemical intermediates.
In U.S. Pat. No. 4,148,920 L- and DL-phenylglycines of the formula ##STR2## where R.sub.1 is hydrogen or methyl and R.sub.2 is NH.sub.2, OH or completes a carboxylic ester group are disclosed as useful in treating diseases and conditions characterized by reduced blood flow, oxygen availability or reduced carbohydrate metabolism in the cardiovascular system. The D-isomers are disclosed as inactive.